APASL2017 [OP115] 替诺福韦治疗减少肝细胞癌 和肝硬化的慢性乙

StephenW

APASL2017[OP115]
Tenofovir treatment reduces hepatocellular carcinoma
and deaths in chronic hepatitis B patients with liver cirrhosis
Ken Liu1,2, Jonggi Choi3, Vincent Wai-Sun Wong1, Young-Suk
Lim3, Grace Lai-Hung Wong1
1Institute of Digestive Disease, The Chinese University of Hong
Kong, Hong Kong; 2Faculty of Medicine, The University of Sydney,
Sydney, Australia; 3Asan Medical Center, University of Ulsan
College of Medicine, Ulsan, South Korea
Background: Antiviral therapies such as lamivudine and entecavir
have been shown to reduce hepatocellular carcinoma (HCC) development
and death in chronic hepatitis B (CHB) patients with
cirrhosis. Tenofovir disoproxil fumarate (TDF) is a potent antiviral
agent with no documented resistance to date, but its impact on clinical
outcomes is unclear. We aimed to investigate the efficacy of TDF
therapy on HCC and deaths.
Methods: Two cohorts of CHB cirrhotic patients were retrospectively
studied. Cirrhosis was defined by liver histology, thrombocytopenia
(\150 9 109/L) or features of portal hypertension seen on imaging.
TDF cohort included consecutive patients from two Asian centres
who had received TDF 300 mg/day for at least 12 months. Control
cohort included historical untreated patients who underwent routine
clinical care. The 5-year cumulative probabilities of HCC, all-cause
mortality and liver-related mortality were compared.
Result: 773 TDF-treated (68% men; age 52 ± 9 years; follow-up
38 ± 9 months; 48% hepatitis B e antigen [HBeAg] positive) and 69
untreated cirrhotic patients (80% men; age 51 ± 11 years; follow-up
96 ± 45 months; 28% HBeAg positive) were studied. The median
model for end-stage liver disease (MELD) score and interquartile
range (IQR) for TDF vs. control cohorts were 8 (IQR 7–9) vs. 9
(7–12), respectively. The frequencies of patients with undetectable
hepatitis B virus (HBV) DNA in TDF cohort at baseline,
years 1, 2 and 3 were 13.8, 80, 86 and 84%, respectively. At the
5-year follow-up mark, there were 69 HCCs and 27 deaths of which
23 were liver-related. The 5-year cumulative probabilities in TDF vs.
control cohort were: 13.5% (95% confidence interval [CI] 2.9–24.0%)
vs. 26.4% (15.2–37.6%) for HCC (P = 0.001); 2.9% (0.0–6.8%) vs.
23.3% (12.9–33.7%) for liver-related mortality (P\0.001) and 2.9%
(0.0–6.8%) vs. 28.2% (17.4–39.0%) for all-cause mortality
(P\0.001), respectively (Fig. 1). On multivariate Cox regression
model, TDF-treated patients had reduced risks of HCC (hazard ratio
[HR] 0.52, 95% CI 0.28–0.97, P = 0.039), liver-related mortality
(HR 0.15, 95% CI 0.06–0.41, P\0.001) and all-cause mortality (HR
0.12, 95% CI 0.05–0.30, P\0.001) at 5 years after adjustment for
age, sex, MELD score and prior antiviral treatment experience
(Table 1). Increased serum albumin was also an independent protective
factor for these events.
Conclusion: TDF treatment reduces risks of HCC, liver-related and
all-cause mortality in CHB patients with cirrhosis in 5 years.

StephenW

APASL2017 [OP115]
替诺福韦治疗减少肝细胞癌
和肝硬化的慢性乙型肝炎患者的死亡
Ken Liu1,2，Jonggi Choi3，Vincent Wai-Sun Wong1，Young-Suk
Lim3，Grace Lai-Hung Wong1
1摘要：目的探讨消化道疾病的临床特点
香港; 2悉尼大学医学院，
悉尼，澳大利亚; 3蔚山大学亚松医学中心
韩国蔚山医学院
背景：抗病毒治疗如拉米夫定和恩替卡韦
已显示减少肝细胞癌（HCC）发展
和死亡的慢性乙型肝炎（CHB）患者
肝硬化。替诺福韦地索普西富马酸盐（TDF）是一种有效的抗病毒药物
药物没有记录的抗药性，但其对临床的影响
结果不清楚。我们的目的是调查TDF的疗效
治疗HCC和死亡。
方法：回顾性分析两组CHB肝硬化患者
研究。肝硬化定义为肝组织学，血小板减少
（\ 150 9 109 / L）或在成像上看到的门静脉高压的特征。
TDF队列包括来自两个亚洲中心的连续患者
其已经接受TDF 300mg /天至少12个月。控制
队列包括历史未经治疗的患者进行常规
临床护理。肝癌的5年累积概率，全因
比较死亡率和肝相关死亡率。
结果：773 TDF治疗（68％男性;年龄52±9岁;随访
38±9个月; 48％乙型肝炎e抗原[HBeAg]阳性）和69
未治疗的肝硬化患者（80％男性;年龄51±11岁;随访
96±45个月; 28％HBeAg阳性）。中位数
终末期肝病（MELD）评分和四分位间的模型
TDF与对照组的范围（IQR）分别为8（IQR 7-9）与9
（7-12）。患者的频率不可检测
乙型肝炎病毒（HBV）DNA在基线的TDF队列，
年1,2和3分别为13.8,80,86和84％。在
5年随访，69例HCC和27例死亡
23是肝相关的。 TDF的5年累积概率
对照组为：13.5％（95％置信区间[CI] 2.9-24.0％）
与HCC的26.4％（15.2-37.6％）（P = 0.001）; 2.9％（0.0-6.8％）vs.
，肝脏相关死亡率为23.3％（12.9-33.7％）（P <0.001）和2.9％
（0.0-6.8％），而全因死亡率为28.2％（17.4-39.0％）
（P \ 0.001）（图1）。多变量Cox回归
模型，TDF治疗的患者具有降低的HCC风险（风险比
[HR] 0.52,95％CI 0.28-0.97，P = 0.039），肝相关死亡率
（HR 0.15,95％CI 0.06-0.41，P <0.001）和全因死亡率（HR
0.12，95％CI 0.05-0.30，P <0.001）
年龄，性别，MELD评分和以前的抗病毒治疗经验
（表格1）。增加的血清白蛋白也是独立的保护性
这些事件的因素。
结论：TDF治疗降低肝癌的风险，与肝相关
CHB肝硬化患者5年的全因死亡率。